Knowledge of the evolution of physiological mechanisms is necessary for inferring the genetic organization that underlies the complex events of human development and differentiation, for understanding present-day structure-function relationships, and for designing rational therapies to correct derangements of normal development. We propose to identify and characterize homologous (evolutionarily related) physiological mechanisms or systems that are operative in the human body at various stages of development or in different tissues. Homologous mechanisms have component parts that are structurally related and usually function similarly and in the same order with respect to each other. To identify related protein sequences in the accumulating data, we will use a variety of computer-assisted survey and statistical evaluation procedures. Having shown that parts of two or more physiological mechanisms are homologous, we will investigate their evolutionary history to discern the functional and structural characteristics of the ancestral mechanism, to trace the changes that produced the present-day functional differences, and to estimate when the genetic duplications that produced these related mechanisms occurred. Evolutionary trees constructed from protein sequences will illuminate the development of differentiated cell types, of complex metabolic pathways, and of key control systems, the cell membrane receptor proteins, the contractile system proteins, the self-identification proteins for the whole organism and for various tissues, and the immune system proteins. BIBLIOGRAPHIC REFERENCES: Barker, W.C., and Dayhoff, M.O., "Structural and genetic relationships among human lipoproteins", Biophys. J., Vol. 16, p.9a, 1976 (abstract).